Regional myocardial contraction diminishes immediately after the onset of ischemia. There is a concurrent slowing of aerobic ATP synthesis while catabolism continues, leading to decreased ATP content. Even if perfusion is restored before cell death, myocardial dysfunction is prolonged. Our hypothesis is that ATP repletion is slow, and is the limiting factor in the return of myocardial function after an ischemic episode. The model chosen to test this hypothesis is the intact open-chested dog. Adenine nucleotide (AN) content will be measured during control, after 10 min. of ischemia, and during reperfusion. This will be done by taking repetitive myocardial biopsies (10-15 micrograms) of the area subjected to ischemia. Creatine phosphate (CP) will also be measured in these same samples to assess the integrity of the mitochondria. Regional myocardial function will be evaluated with ultrasonic dimension transducers. The relationship between myocardial function and AN content can then be assessed. If AN repletion and return of function are both delayed, as suggested from preliminary data and results in the literature, we will attempt to accelerate purine nucleotide synthesis by two interventions: ribose infusion to increase phosphoribosylpyrophosphate content, and administration of amino-imidazole-carboxamide ribonucleoside, an intermediate in the de novo pathway of purine synthesis. The effect of pretreatment with these compounds on AN content and myocardial function during recovery from ischemia will be compared with the results from untreated animals. If myocardial function can be improved by increasing AN content, then one can conclude that AN content is a determinant of myocardial function and we will have provided strong support for the hypothesis stated above. If this hypothesis is confirmed, the results may lead to the clinical testing of interventions designed to increase the AN content of the heart. This is turn may lead to improvements in regional myocardial function in patients recovering from myocardial ischemia.